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111.
Activation of microglial cells and complement following traumatic injury in rat entorhinal-hippocampal slice cultures 总被引:4,自引:0,他引:4
The complement cascade has been suggested to be involved in development of secondary brain damage following traumatic brain injury (TBI). Previous studies have shown that reactive microglia are involved in activation of the complement cascade following various injuries to the nervous system. Macrophages seem to have a significant role in this process, but it is still unclear whether these cells, as well as the complement components, are derived from reactive microglia or if these biological events only can occur as a result from the influx of plasma and monocytes via a disrupted blood-brain barrier (BBB). The aim of this study was to investigate the response of microglial cells and the complement system in the absence of plasma/blood components following a standardized crush injury in an entorhinal-hippocampal slice culture. There was a clear increase in complement component C1q and C5b-9-IR (Membrane Attack Complex, MAC) in the area near the crush injury. MAC-IR appeared as numerous dots in clusters which co-localized with anti-NeuN labelled neurons in the injury border zone. Complement C1q-IR co-localized with reactive microglia, co-labelled with OX42 antisera. These findings show activation of the complement cascade near the injury zone and in particular, formation of MAC at the surface of neurons in this area. There was a distinct activation of microglial cells (OX42-IR) near the site of injury, as well as an increase in ED-1 expressing macrophages. In the absence of blood and plasma components it is likely that ED-1-labelled cells represent reactive microglia transformed into macrophages. In addition, Neurons (Neun-IR) near the injury were found to co-localize with clusterin-IR indicating upregulation of a defense system to the endogenous complement attack. The present study provides evidence that microglia and complement is activated in the injury border zone of the tissue slice in a similar fashion as in vivo following TBI, despite the absence of plasma/blood products and cells. These findings support the hypothesis that reactive microglia have a key role in complement activation following TBI by local synthesis of complement with a potential impact on development of secondary neuronal insults. 相似文献
112.
Fored CM Nise G Ejerblad E Fryzek JP Lindblad P McLaughlin JK Elinder CG Nyrén O 《Journal of the American Society of Nephrology : JASN》2004,15(1):180-186
Exposure to organic solvents has been suggested to cause or exacerbate renal disease, but methodologic concerns regarding previous studies preclude firm conclusions. We examined the role of organic solvents in a population-based case-control study of early-stage chronic renal failure (CRF). All native Swedish residents aged 18 to 74 yr, living in Sweden between May 1996 and May 1998, formed the source population. Incident cases of CRF in a pre-uremic stage (n = 926) and control subjects (n = 998), randomly selected from the study base, underwent personal interviews that included a detailed occupational history. Expert rating by a certified occupational hygienist was used to assess organic solvent exposure intensity and duration. Relative risks were estimated by odds ratios (OR) in logistic regression models, with adjustment for potentially important covariates. The overall risk for CRF among subjects ever exposed to organic solvents was virtually identical to that among never-exposed (OR, 1.01; 95% confidence interval [CI], 0.81 to 1.25). No dose-response relationships were observed for lifetime cumulative solvent exposure, average dose, or exposure frequency or duration. The absence of association pertained to all subgroups of CRF: glomerulonephritis (OR, 0.96; 95% CI, 0.68 to 1.34), diabetic nephropathy (OR, 1.02; 95% CI, 0.74 to 1.41), renal vascular disease (OR, 1.16; 95% CI, 0.76 to 1.75), and other renal CRF (OR, 0.92; 95% CI, 0.66 to 1.27). The results from a nationwide, population-based study do not support the hypothesis of an adverse effect of organic solvents on CRF development, in general. Detrimental effects from subclasses of solvents or on specific renal diseases cannot be ruled out. 相似文献
113.
OBJECTIVE: The etiology of secretory otitis media (SOM) is multifactorial. The main factors discussed are infection and tubal dysfunction. This study aimed to detect poor tubal function and tympanic membrane pathology in young adults after extremely long-standing SOM. METHODS: Thirty-four patients, 16-25 years old, with previous chronic SOM persisting at least 6 years (mean 11.2 years, range 6.2-18.6 years), were retrospectively examined at a mean of 18 years after their first myringotomy or tube insertion and comparison was made with 15 controls. The medical records were scrutinized, otomicroscopic examination was performed and the Eustachian tube function was studied in a mini pressure chamber. RESULTS: The mean age at SOM onset was 2.4 years (range 0.5-8.4 years) and the mean period from the last myringotomy or when the last tube had disappeared to follow-up was 6.7 years (range 1.3-12.8 years). Tympanic membrane pathology was found in 76% of the ears of SOM patients and in none (0%) of controls (P<0.001). The youngest patients had more atrophy than the older patients (P<0.05) and more myringosclerosis was observed in patients with shorter interval between SOM ending and examination. The patients were found to have significantly poorer active tubal function; i.e. higher inability to equilibrate negative or negative and positive middle ear pressure, compared with controls (P<0.001). The majority of the patients (74%) still experienced some kind of discomfort in their ears at the time of examination. CONCLUSIONS: Still in adulthood patients with chronic SOM during childhood exhibit dysfunction of the tube and tympanic membrane pathology to a high extent. 相似文献
114.
115.
The health risk of smoking is valued using the contingent valuation method, applied to a Swedish sample of smokers. The respondents were asked to put a value on newly developed cigarettes with no associated health risks. The average additional willingness to pay for the new cigarettes is estimated to be between 10 and 41 SEK per pack, where the variation is due to statistical method, discounting, and whether the open-ended or closed-ended question format is used. Using medical data on life shortening effects of smoking, the results indicate rather low values put on a lost life-year, compared to most existing estimates based on other methods. This may indicate that smokers do underestimate the health risk of smoking. There is also initial optimism-bias regarding people's own ability to quit smoking at will. However, there are remaining methodological questions and we found little or no sensitivity to scope. 相似文献
116.
A missense mutation in GUCY2D acts as a genetic modifier in RPE65-related Leber Congenital Amaurosis
Silva E Dharmaraj S Li YY Pina AL Carter RC Loyer M Traboulsi E Theodossiadis G Koenekoop R Sundin O Maumenee I 《Ophthalmic genetics》2004,25(3):205-217
Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous severe retinal dystrophy presenting in infancy. To explain the phenotypical variability observed in two affected siblings of a consanguineous pedigree diagnosed with LCA and establish a genotype-phenotype correlation, we screened GUCY2D, RPE65, CRX, AIPL1, and RPGRIP1 for mutations. The more severely affected sibling carried a heterozygous missense mutation in the GUCY2D gene (Ile539Val), which did not segregate with the disease phenotype. Subsequently, a homozygous nonsense mutation (Glu102STOP) in the RPE65 gene was identified in both affected siblings, thus identifying the causative gene. This data provides evidence for the presence of genetic modulation in LCA. It appears that the heterozygous GUCY2D mutation further disrupts the already compromised photoreceptor function resulting in more severe retinal dysfunction in the older sibling. We suggest that the unusual phenotypic variability in these two siblings with LCA is caused by the modifying effect of a heterozygous GUCY2D mutation observed against the disease background of a homozygous RPE65 mutation. 相似文献
117.
118.
Richiardi L Akre O Montgomery SM Lambe M Kvist U Ekbom A 《Journal of the National Cancer Institute》2004,96(2):145-147
Previous studies have suggested an association between subfertility and testicular cancer by using fecundity and semen characteristics to measure fertility. The occurrence of twinning in offspring may be used to investigate male reproductive health, because dizygotic twinning is reduced by male subfertility. We therefore assessed number of children and offspring twinning rates among 4592 Swedish patients with testicular cancer and 12 254 control subjects. Before diagnosis, case patients had a decreased number of children (for testicular cancer, odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.62 to 0.81; at least three children compared with no children), with a lower frequency of dizygotic twinning (for unlike-sex twins, OR for the father having testicular cancer = 0.49, 95% CI = 0.22 to 1.08). The ratio of unlike-sex to same-sex twins was 0.22 among children of case patients and 0.66 among children of control subjects (adjusted P =.03, two-sided Wald test). We also found an increased occurrence of twinning after diagnosis, probably attributable to treatment for iatrogenic subfertility. Our study strongly supports evidence of an association between subfertility and the subsequent risk for testicular cancer. 相似文献
119.
Mercer A Rönnholm H Holmberg J Lundh H Heidrich J Zachrisson O Ossoinak A Frisén J Patrone C 《Journal of neuroscience research》2004,76(2):205-215
In recent years, it has become evident that neural stem cells in the adult mammalian brain continuously generate new neurons, mainly in the hippocampus and olfactory bulb. Although different growth factors have been shown to stimulate neurogenesis in the adult brain, very little is known about the role of neuropeptides in this process. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with pleiotropic effects acting through three receptors to which it has high affinity, namely, PACAP receptor 1 (PAC1), vasoactive intestinal peptide (VIP) receptor 1, and VIP receptor 2. We show that PAC1 is expressed in the neurogenic regions of the adult mouse brain, namely the ventricular zone of the lateral ventricle and the hippocampal dentate gyrus. Cultured neural stem cells isolated from the lateral ventricle wall of adult mice express PAC1 and proliferate in vitro in response to two PAC1 agonists, PACAP and Maxadilan, but not VIP at physiologic concentrations, indicating PAC1 as a mediator of neural stem cell proliferation. Pharmacologic and biochemical characterization of PACAP-induced neural stem cell proliferation revealed the protein kinase C pathway as the principal signaling pathway, whereas addition of epidermal growth factor synergistically enhanced the proliferating effect of PACAP. Further in vitro characterization of the effect of PACAP on neural stem cells showed PACAP capable of stimulating ex novo in vitro formation of multipotent neurospheres with the capacity to generate both neuronal and glial cells. Finally, intracerebroventricular infusion of PACAP increases cell proliferation in the ventricular zone of the lateral ventricle and the dentate gyrus of the hippocampus. We conclude that PACAP, through PAC1, is a potent mediator of adult neural stem cell proliferation. 相似文献
120.
Heilig M Zachrisson O Thorsell A Ehnvall A Mottagui-Tabar S Sjögren M Asberg M Ekman R Wahlestedt C Agren H 《Journal of psychiatric research》2004,38(2):113-121
Extensive animal studies suggest neuropeptide Y (NPY) to be involved in coping with a wide range of stressors, and that impaired central NPY signalling could be involved in the pathophysiology of anxiety and depression. Human studies of central NPY levels in depression have, however, been inconclusive. Here, we examined levels of NPY-like immunoreactivity (NPY-LI) in the cerebrospinal fluid (CSF) of medication-free subjects with treatment refractory unipolar depression. Patients were admitted to a research inpatient unit, examined under standardized conditions, and compared with a sample of volunteers in whom psychiatric morbidity was excluded. A robust suppression of NPY levels in patient CSF was found, while other putative CSF markers (monoamine metabolites, somatostatin) did not differ between the groups. We then explored whether this finding might be related to a recently described T1128C coding polymorphism which results in a Leu7-> Pro7 substitution of the signal peptide, and a previously not described T -399C polymorphism in the promoter region of the preproNPY gene. Preliminary evidence was found for an association of both markers with a diagnosis of depression, indicating the possibility of an underlying haplotype influencing the vulnerability for developing depressive illness. Our present findings are in line with an extensive animal literature, and further support the notion that impaired NPY function could contribute to depressive illness. 相似文献